In the production of large, complex therapeutic proteins, animal cells are preferred as the biocatalyst. Various types of production bioreactors are employed including deep-stirred and sparged tanks (with or without microcarriers), cell-immobolizing matrices, and fluidized beds of porous microcarriers. We have invented a new cell-retention technique using a centrifuge to remove and return living cells from the harvest to the bioreactor. According to the literature, this is a first-time achievement. Preliminary tests indicate high cell density, viability, cell-specific productivity relative to other animal-cell bioreactors. The objective of this Phase I proposal is to test this invention beyond the single cell line that has been tested, in the laboratory to establish its feasibility as an economically important bioreactor for large-scale animal-cell culture in the production of therapeutic proteins. An extension of the work in Phase II will confirm its economic value at beta-sites in the biopharmaceutical industry and will extend its application to plant and insect cells. In Phase III, the centrifugal cell-retention bioreactor will be commercialized to become an important new bioprocessing tool.